Viruses that infect multiple phylogenetically distant hosts, for example hosts from different kingdoms, phyla, or classes, must accommodate the differences in the hosts so that the virus can efficiently replicate in hosts with different biochemical and molecular processes. These host differences include, for example, thermoregulation, protein glycosylation patterns, biochemical features of cell membranes, and CpG dinucleotide frequencies. Arboviruses, for example, have the ability to infect vertebrate and arthropod hosts.
The term arbovirus (arthropod-borne virus) applies to any virus that is transmitted to humans and/or other vertebrates by certain species of blood-feeding arthropods, chiefly insects (flies and mosquitoes) and arachnids (ticks). Families in the current classification system that have some arbovirus members include Bunyaviridae (comprising the bunyaviruses, phleboviruses, nairoviruses, and hantaviruses), Flaviviridae (comprising only the flaviviruses), Reoviridae (comprising the coltiviruses and orbiviruses), and Togaviridae (comprising the alphaviruses). Birds are often reservoirs for arboviruses, which are transmitted by mosquitoes to horses, other domestic animals, and humans. Certain arboviruses are transmissible by humans, including dengue fever, yellow fever, and chikungunya disease, which can be transmitted from person to person via mosquitoes.
Dengue virus (DENV) is an enveloped, plus stranded RNA arbovirus (genome ˜11 kb) of the genus Flavivirus of the Flaviviridae family. DENV is primarily transmitted by the urban-adapted Aedes aegypti mosquito vector that has become widely distributed in tropical and subtropical regions. The diseases resulting from DENV infection include self-limiting dengue fever (DF), life-threatening dengue shock syndrome (DSS), and dengue hemorrhagic fever (DHF) characterized by increased vascular permeability and thrombo-cytopenia. DENV infections are one of the leading causes of arthropod-borne human diseases in the world. Each year there is an estimated 50-200 million DENV infections world-wide, resulting in 500,000 cases of DHF/DSS, and over 20,000 deaths, with 3.6 billion people at risk.
There are five antigenically distinct serotypes of DENV. Infection with one serotype induces immunity against that serotype and some degree of cross-protection against the other serotypes. However, the cross-protective immunity typically persists only for a relatively short time. Also, cross-reactive antibodies may bind to, but not neutralize other serotypes, leading to more severe secondary infections. An effective dengue vaccine would preferably be protective against all known serotypes. Currently, there are no marketable vaccines available capable of preventing human infection by any of the DENV serotypes.
Codon pair preference, or codon pair bias, refers to a phenomenon in which certain pairs of adjacent codons are used more frequently or less frequently in a particular host than expected after accounting for the frequency of usage of the individual codons (Gutman & Hatfield, 1989; Moura et al., 2007; Coleman et al., 2008). Every codon pair can be assigned a codon pair score (CPS), which is the natural logarithm of the ratio of the observed frequency of the codon pair to the expected frequency of the codon pair (i.e., CPS=ln(Observed/Expected) (Coleman et al., 2008).